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LRRC8A在血管新生中的作用及其机制.docx

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LRRC8A在血管新生中的作用及其机制 Title:TheRoleandMechanismsofLRRC8AinAngiogenesis Abstract: Angiogenesis,theformationofnewbloodvesselsfrompre-existingones,playsacriticalroleinvariousphysiologicalandpathologicalprocesses.Understandingtheunderlyingmechanismsofangiogenesisiscrucialforthedevelopmentoftherapeuticinterventionsfordiseasessuchascancer,cardiovasculardisorders,anddiabeticretinopathy.Leucine-richrepeat-containingprotein8A(LRRC8A)hasemergedasakeyregulatorofcellvolumehomeostasisandhasbeenrecentlyimplicatedinangiogenesis.ThisreviewaimstoexploretheroleandmechanismsbywhichLRRC8Aregulatesangiogenesis. Introduction: Angiogenesisisacomplexprocessinvolvingtheproliferation,migration,anddifferentiationofendothelialcells,whicheventuallyformnewbloodvessels.Dysregulationofangiogenesisunderliesthepathogenesisofseveraldiseasessuchascancer,oculardisorders,andcardiovasculardiseases.LRRC8AisatransmembraneproteinthatformsaheteromericcomplexcalledtheVolume-RegulatedAnionChannel(VRAC).Apartfromitsroleincellvolumeregulation,recentevidencesuggeststhatLRRC8Aalsoparticipatesinangiogenesis. RoleofLRRC8AinAngiogenesis: LRRC8Ahasbeenshowntopromoteangiogenesisbyenhancingendothelialcellproliferation,migration,andtubeformation.KnockdownofLRRC8Ainendothelialcellsresultedindecreasedangiogenicpotential,suggestingitsimportanceinpromotingangiogenesis.Additionally,LRRC8Awasfoundtobeupregulatedintheendothelialcellsofnewlyformedbloodvesselsinvariouspathologicalconditions,furthersupportingitsroleinangiogenesis. MechanismsofLRRC8AinAngiogenesis: 1.Regulationofcellvolume: LRRC8AisakeycomponentoftheVRAC,whichplaysacriticalroleinmaintainingcellularvolumehomeostasis.Changesincellvolumehavebeenshowntoinfluencevariousangiogenicprocesses,includingendothelialcellmigrationandtubeformation.LRRC8A-mediatedregulationofcellvolumecould,therefore,indirectlyinfluenceangiogenesis. 2.Modulationofiontransport: LRRC8Aformsanionchannelcomplexthatfacilitatesthetransportofchlorideionsacrossthecellmembrane.Chloridechannelshavebeendemonst